DETERMINANTS OF CARDIAC FIBROSIS IN EXPERIMENTAL HYPERMINERALOCORTICOID STATES

Uninephrectomized rats maintained on 1.0% Nacl to drink and infused wi th aldosterone (0.75 mu g/h) for 8 wk have previously been shown to de velop hypertension, cardiac hypertrophy, and cardiac fibrosis. In the present study we have shown that K+ supplementation (1.0% NaCl plus 0. 4% KCI drinking solution) alters neither the interstitial nor the peri vascular fibrotic response to mineralocorticoid treatment. Second, rat s receiving 0.75 mu g/h 9 alpha-fluorocortisol, a mineralocorticoid an d glucocorticoid agonist, respond with hypertension and cardiac fibros is without cardiac hypertrophy. Finally, intracerebroventricular infus ion of the mineralocorticoid receptor antagonist RU-28318 blocks blood pressure elevation, but not cardiac hypertrophy or fibrosis, when ald osterone is coinfused peripherally. We conclude that the myocardial fi brosis observed in response to chronic mineralocorticoid elevation and salt loading is a humorally mediated event independent of hypokalemia , hypertension, and cardiac hypertrophy. It remains to be determined w hether the fibrosis observed in the presence of excess salt represents a direct (e.g., cardiac) effect of mineralocorticoid hormones or one mediated via a primary action on classical epithelial aldosterone targ et tissues (e.g., kidney).